The role of acid cholesterol esterase (ACE) in the metabolism of intracellular cholestrol ester was evaluated in patients with premature cardiovascular disease. Acid cholesterol esterase activity, assayed in the lymphocytes of 36 patients, aged 25-45, with angiographically documented coronary artery disease, was significantly lower than that measured in 35 patients of similar age referred for evaluation of non-atherosclerotic heart disease. Multivariant analysis showed the reduction in ACE in the coronary artery group to be significant and independent of the incidence of any other recognized risk factor. Deficiency in cellular ACE, by limiting hydrolysis of intracellular cholesterol ester, may act as an independent risk factor in the atherogenic process.